J Neural Transm (1992) [Suppl] 35: 71-83

© Springer-Verlag 1992

Cortical and thalamic lesions in rats with genetic absence epilepsy M. Vergnes and C. Marescaux Laboratoire de Neurophysiologie et Biologie des Comportements, Centre de Neurochimie du CNRS, Strasbourg, France

Summary. In generalized, non-convulsive, absence epilepsy, spike-andwave discharges (SWD) are recorded in both the cortex and the thalamus. The effect of various cortical and thalamic lesions on the occurrence of spontaneous SWD was examined in rats from a strain with genetic absence epilepsy. Cortical ablations suppressed SWD recorded in the thalamus. KCI induced unilateral cortical spreading depression and transiently suppressed SWD in the ipsilateral cortex and thalamus; SWD recovered simultaneously in both structures. Bilateral thalamic lesions of the anterior nuclei, the ventromedial nuclei, the posterior area, or lesion of the midline nuclei did not suppress cortical SWD. However, large lesions of the lateral thalamus, including the specific relay and reticular nuclei, definitely suppressed ipsilateral SWD, and pentylenetetrazol, THIP or gammabutyrolactone failed to restore the cortical SWD. These results demonstrate that the neocortex and the specific thalamic nuclei are both necessarily involved in the generation of SWD in absence epilepsy. Introduction Epileptic seizures typical of generalized, non-convulsive epilepsy occur spontaneously in a strain of Wistar rats selected in our laboratory and called "genetic absence epilepsy rats from Strasbourg" (GAERS). Behavioral, electroencephalographic (EEG), pharmacological and genetic characteristics are similar to those of the human disease, also termed petit mal or absence epilepsy (Vergnes et aI., 1982, 1990). During the seizures, which occur spontaneously in waking animals, bilaterally synchronous spike and wave discharges (7-10c/s, mean duration 20s/min) are recorded from the EEG of these animals. In addition, localized EEG recordings from various brain regions have shown a predominance of the SWD in the neocortex and thalamus. The SWD were particularly large in the frontoparietal cortex and

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the relay nuclei of the lateral thalamus (Vergnes et aI., 1987), suggesting that these structures play a predominant role in the development of SWD . . In humans, SWD were similarly recorded over the cortex and in the thalamus (Williams, 1953). These data are in agreement with electrophysiological results observed in generalized epilepsy induced by penicillin in the cat (Avoli and Gloor, 1982; Avoli et aI., 1983; Mc Lachlan et aI., 1984). In this feline model, cortical and thalamic structures were shown to be intimately associated in the generation of SWD. In the present experiments various cortical and thalamic areas were lesioned in GAERS to ascertain which structures are essential to the occurrence of spontaneous SWD and to characterize cortico-thalamic relationships in the generation of SWD. Since the reciprocal thalamo-cortical connections are ipsilateral, the effect of a cortical or a thalamic lesion is reflected in the EEG of the ipsilateral thalamus or cortex respectively. In order to prevent the spread of the SWD from one hemisphere to the other (Vergnes et aI., 1989), the corpus callosum was transected in animals with unilateral lesions, the unlesioned side serving as a control.

Cortical lesions

The cortex was lesioned in two different ways. In the first series of experiments, cortical ablation was performed by suction. With this technique the lateral parts of the cortex cannot be removed completely without also damaging neighboring structures. In the second group of experiments a functional and acute elimination of the cortex was effected, by local application of a KCI solution, which induces a spreading depression that extends transiently all over the cortex (Bures et aI., 1974).

Cortical ablation

Methods Six male animals of the GAERS strain were anesthetized with pentobarbital (40 mg/kg ip) and placed in a stereotaxic apparatus. The bone overlying the cortex was removed with a dental drill, preserving the midline skull and a small strip of bone through which the ipsilateral thalamic electrode had to be lowered. The dorsal part of the cortex was extensively removed over the right hemisphere, by suction through a pipette connected to a water pump. A bipolar electrode made of twisted enameled stainless steel, with 1 mm dorsoventral distance between the two poles, was then placed stereotoxically into the lateral thalamus at the following coordinates in mm, with reference to lambda: AP = 5, ML = 2, DV = 6,5. On the opposite side, two single

Cortex and thalamus lesions in rats with absence epilepsy

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contact electrodes were screwed into the skull over the fronto-parietal cortex. All electrodes were connected to a micro connector and embedded in acrylic cement. The animals were treated with a single injection of extencillin to prevent infection. The cortical and thalamic EEG was recorded regularly during the two postoperative months. At the end of that time, the animals were killed with an overdose of pentobarbital. The brains were removed and serial brain slices were prepared for histological control of lesion and electrode location. Results In all animals SWD were absent in the right thalamus following the ipsilateral decortication. On the opposite non lesioned side, the SWD appeared normal. In 4 animals, the SWD reappeared in the right thalamus between the 15th and 30th day after cortical lesioning. The SWD usually occurred separately in the right and left hemisphere, this interhemispheric desynchronization resulting from an associated damage to the corpus callosum. In two animals no SWD were recorded in the right thalamus during the 2 months of survival, and the baseline EEG was apparently normal with fast low voltage activity. Histology The recording electrodes were well localized in the ventrolateral thalamus. The frontal cortex was almost completely removed in all animals. The parietal cortex was removed dorsally but was spared laterally to various extents. The lesion also involved the dorsal occipital cortex. The suppression of ipsilateral thalamic SWD was related to the extent of the cortical lesion, especially of the lateral parietal cortex, the rats which recovered SWD having the smallest lesions. The corpus callosum was damaged in all animals. In addition, damaged neurons were found in lateral relay nuclei at a distance from the cortical lesion. These lesions probably resulted from retrograde degeneration of thalamic neurons projecting to the lesioned cortex. Cortical spreading depression

Methods Two male rats of the GAERS strain were used. First, the corpus callosum and medial thalamus were transected with a small surgical blade mounted

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on a stereotaxic holder. After removal of the midline skull with a dental drill, the blade was lowered at AP = 2, DV = 4 (coordinates in mm with the lambda as reference) into the midline of the brain and then moved anteriorly to AP = 4.5, where it was lowered to DV = 7 and moved to AP = 7. The blade was then raised to DV = 4.5, moved to AP = 12, and removed dorsally. After one week's recovery the rats were implanted bilaterally with a bipolar electrode in the lateral thalamus (AP = 6, ML = 2.5, DV = 6.5), two single contact electrodes over the cortex (AP = 10.5 and 4, ML = 3) and a stainless-steel guide cannula (AP = 8, ML = 4, DV = 1; OD = 0.4, ID = 0,3), which was attached to the connector and was also used as a cortical electrode. Stylets of the same length were left in place in the cannula and were replaced for injections by an inner cannula with a smaller diameter (OD = 0.28, ID = 0.18), but the same length as the guide cannula. Doses of 1 or 0.5111 25% KCl solution, or 0.9% CINa as control, were injected unilaterally at a rate of 1 Ill/min with a micro syringe (Hamilton, 1111) through polyethylene tubing fixed to the injection cannula, which was left in place for 30 s after the completion of the injection. The rat was gently immobilized during the injection, then immediately connected to the recording apparatus (Alvar), and the EEG was recorded. In further experiments the animals were pretreated with drugs which potentiate SWD (Vergnes et aI., 1984; Warter et aI., 1988; Depaulis et aI., 1988). THIP, a GABA A agonist (7.5 mg/kg), haloperidol, a dopamine antagonist (1 mg/kg) or gamma-butyrolactone, an agonist of gammahydroxybutyrate receptors (GBL, 250mg/kg) was injected ip. When the SWD became permanent, 1111 of KCl solution was applied unilaterally on the cortex. After 6 months' survival, the animals were killed and the brains processed for histological examination. Results The SWD recorded from the left and right cortex and thalamus were completely dissociated as a consequence of the medial transection. They occurred independently and were totally asynchronous in both hemispheres. In contrast, the SWD were synchronized and simultaneous in the cortex and thalamus of the same hemisphere (Fig. 1). Each animal received four unilateral cortical injections of 0.5 or 1111 of KCl solution through each cannula. KCl application provoked an immediate flattening of the ipsilateral cortical EEG, whereas the thalamic baseline EEG appeared normal. A total suppression of the SWD was obtained on that side in both cortex and thalamus (Fig. 1). The EEG and SWD on the contralateral side were unchanged. The cortical EEG on the injected side recovered first with slow waves and then progressively with appearance of increasing frequencies. The EEG appeared normal after a period of 10 to 20 min. However, SWD reappeared only later, after delays varying from 37

75

Cortex and thalamus lesions in rats with absence epilepsy

A R.Cx

1:

R. ThaI. 'r , LCx L ThaI.

B .'

J

c

~--~----~~,~.,~-~~.~~-.----------,~~~

iJ

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Fig. 1. EEG recorded simultaneously in the right cortex (R. Cx), right thalamus (R. ThaI), left cortex (L. Cx) and left thalamus (L. ThaI) in a rat with a transection of the corpus callosum and the midline thalamus. A Control EEG showing the dissociation of the SWD in the left and right hemisphere. B 5 min after application of 1 III of KCI solution on the right cortex producing a spreading depression over the right cortex. SWD are suppressed in both the right thalamus and cortex. In the left thalamus and cortex SWD are unchanged. C 40 min after the spreading depression the first SWD reappears simultaneously on the right cortex and thalamus. Calibration 1 s., 200 IlV

to 40 min after injection of 0.5 J..LI and from 1 to 2 h after injection of 1 J..L1. Recovery of SWD always occurred simultaneously in the ipsilateral cortex and thalamus, starting sometimes with a reduced amplitude in the cortex. No thalamic SWD were observed without a concomitant synchronous oscillation in the cortex (Fig. 1). Control injections of saline suppressed ipsilateral SWD for 3 to 7 min. without altering the baseline EEG. After administration of THIP, haloperidol or GBL, the SWD were much increased in both hemispheres, simultaneously in the cortex and in the thalamus. Cortical application of 1 J..LI KCI solution immediately suppressed the ipsilateral SWD, as previously described, the contralateral

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discharges being unchanged. Recovery occurred after delays varying from 30 min to 2 h simultaneously in the thalamus and the cortex, starting with a reduced amplitude in the cortex. Discussion Functional or destructive elimination of the cortex in GAERS suppressed the occurrence of spontaneous SWD and of SWD aggravated by prior injection of drugs known to increase petit-mal-like seizures, such as GABAmimetics, neuroleptics or GHB-activating compounds (Vergnes et aI., 1984; Water et al., 1988; Depaulis et al., 1988). When a large amount of cortex is destroyed, SWD are no longer recorded from the ipsilateral thalamus, where retrograde lesions develop as the result of decortication (Ross and Ebner, 1990). Recovery of SWD after cortical ablation in some animals is probably due to sparing of the most lateral parts of the cortex and/or reorganization of thalamo-cortical circuits. When a functional lesion is produced by a cortical spreading depression, which is supposed to invade one hemicortex, the SWD are transiently suppressed in the ipsilateral thalamus. Only after full recovery of the cortical activity does the SWD reappear simultaneously in the ipsilateral thalamus and cortex. Similar results were obtained in cats with penicillininduced SWD, which were also suppressed by cortical spreading depression (Gloor et al., 1979; Avoli and Gloor, 1982). These results suggest that SWD in petit-mal-like epilepsy requires the participation of a functional cortex. However, no specific site in the cortex appears to be preferentially involved. The lack of cortical localization was previously shown in animals with multiple cortical implantation: the SWD were recorded all over the cortex. Moreover, the SWD started alternately from different locations, which varied from one seizure to another, with some predominance of the lateral frontoparietal cortex (Vergnes, unpublished results). However, localized lesions within these areas did not definitively suppress SWD, suggesting that no specific cortical area is critically involved in the development of SWD. Thalamic lesions

Methods

Electrolytic lesions (2 rnA for 20 ~ec/site at the cathode) were made at various sites in the thalamus. The stereotaxic coordinates are given in mm, with lambda as reference. Large unilateral or bilateral lesions of the lateral thalamus: AP = 4, 5, 6; ML = 1.5, 2.5, 3.5; DV = 6 - 7. In 4 animals the corpus callosum was also transected (AP 2 - 12; DV 4 - 4.5). Bilateral lesions of the anterior

Cortex and thalamus lesions in rats with absence epilepsy

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thalamus: AP = 5.5; ML = 1, 2, 3; DV = 6 - 7. Bilateral lesions of the ventromedial thalamus: AP = 4.5, 5.5; ML = 1.3; DV = 7.3. Lesions of the medial thalamus: AP = 4,5, 6, 7; ML = 0; DV = 6 - 7. All animals were implanted with 4 single contact electrodes over the fronto-parietal cortex, either immediately or 2 days after the lesion. The cortical left and right EEG was recorded between two ipsilateral electrodes. The general behavior and the weight of the animals were noted. At the end of the experiment the animals were killed with an overdose of pentobarbital. Serial paraffin sections of the brains were stained with cresyl violet for histological control of the lesion. Results

Lateral thalamic lesions In four animals large bilateral lesions of the lateral thalamus were obtained. All animals lost weight as a result of aphagia after the lesion. One died on the 16th and one on the 23th postoperative day. The other two spontaneously recovered feeding and were killed 34 and 56 days after the lesion, when their EEG had become stable. No SWD was ever recorded from the cortex during the survival period. The cortical EEG was first altered, with large slow waves, the voltage of which was reduced over time; however fast activities remained rare. In four animals with bilateral lesions extending only to the most posterior part of the lateral thalamus, the SWD were transiently altered. The lateral thalamus was lesioned unilaterally in six rats, four of them with a prior transection of the corpus callosum. In this latter preparation, the unlesioned hemisphere is considered as control, whereas on the lesioned side the effects of the thalamic lesion can be observed. Moreover, the feeding behavior was not affected in these animals, for 46 days after the lesion. No SWD was recorded from the cortex ipsilateral to the thalamic lesion, which had a slow baseline EEG (Fig. 2D). On the unlesioned side the cortical EEG was normal with many SWD. In the two rats without callosal transection very small SWD on the lesioned side were synchronous with the contralateral ones. Drugs capable of inducing SWD in non-epileptic rats (Marescaux et al., 1984, 1990) were injected ip. in these animals: TRIP (10 mg/kg), GBL (170mg/kg) and pentylenetetrazole (PTZ, 20mg/kg). These drugs consistently produced a significant increase of SWD on the unlesioned side. However, no SWD ever occurred in the cortex ipsilateral to the thalamic lesion (Fig. 3). On the other hand, the injection of a higher dose of PTZ (40mg/kg) provoked clonic movements of the limbs and the body with bilateral paroxysmal discharges on the cortex in unilaterally thalamic-Iesioned animals.

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M. Vergnes and C. Marescaux

A L br~~--~~~~~~------~""~. R~__~__~~~~"~______~~""*

B

o

Fig. 2. Left (L) and right (R) cortical EEG after various thalamic lesions. A Lesion of the medial thalamic nuclei B Bilateral lesion of the ventromedial nucleus C Bilateral lesion of the anterior nuclei D Unilateral lesion of the right lateral thalamus after transection of the corpus callosum

RIght la teral thalamIC lesions

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...............,.......... ...._ _ _ _ _ _..;....._ _ _ _ _-.ae,:...................,.,I,l._.,.,..~

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PTZ 25 mg/kg

--J~~ 'I; \ ~~~~~~~~~~~~"'~.~,~~ ~~-~----~~--~--~----~~--~------~~.-.~.~'--~.~.-+.~,---TH1P 10 mg/kg

GBL 170 mg/kg

Fig. 3. Left (L. Cx) and right (R. Cx) cortical EEG in a rat with callosal transection and a large lesion of the right lateral thalamus. No SWD ever appeared on the right cortex; A before any injection; B after PTZ 25 mg/kg; C after THIP 10 mg/kg; Dafter GBL 170mg/kg. PTZ, THIP and GBL increased SWD duration on the unlesioned side, but never induced SWD on the lesioned side

Cortex and thalamus lesions in rats with absence epilepsy

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Fig. 4. Coronal section showing a unilateral lesion of the lateral thalamus, with a transection of the corpus callosum, which suppressed the SWD on the ipsilateral cortex. Am Amygdala; CM central medial n; Cx Cortex; GP globus pallidus; Hi Hippocampus; ic internal capsule; LH lateral hypothalamus; Re reuniens n; Rt reticular n; VL ventrolateral n. (according to the Atlas of Paxinos and Watson, 1982)

Histological examination of the brains showed extensive lesions of all the lateral part of the anterior to posterior thalamus including the relay nuclei, with partial lesions to the globus pallidus and medial nuclei, in all animals in which SWD were suppressed (Fig. 4). In the cortical projection areas of these thalamic nuclei a suppression of pyramidal cells was apparent. In four animals with lesions restricted to the posterior part of the lateral thalamus, partial damage of the ventroposterolateral nucleus and of the reticular nucleus was observed. Anterior thalamic lesions

In two rats, bilateral lesions of the anterior thalamus only transiently suppressed the SWD, which reappeared two days after lesioning and then occurred normally (Fig. 2C). Histological examination of the brains revealed that the anterior thalamic nuclei were bilaterally destroyed, as well as the fornix and the mamillothalamic tract. The anterior part of the ventrolateral and reticular nucleus was affected. Ventromedial thalamic lesions

In seven rats bilateral lesions of the nucleus ventromedialis and the surrounding area in no way altered the SWD or the baseline EEG (Fig. 2B). The lesions partially or totally affected the nucleus ventromedialis as well as parts of the bordering zona incerta. The mamillothalamic tract was interrupted bilaterally in four rats.

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Medial thalamic lesions . In four rats extensive lesions of the medial thalamic nuclei did not affect SWD which appeared bilateral and synchronous only one day after lesioning (Fig. 2A). The histology showed that these lesions extended to all thalamic nuclei along the midline. In addition, in three rats the lesion damaged the anterior commissure, and in one rat, the anterior part of the mesencephalic central gray was altered.

Discussion The cortical SWD were definitely suppressed after extensive lesioning of the ipsilateral thalamus, including the relay nuclei and the reticular nucleus of the thalamus. The altered cortical EEG with continuous large slow waves gradually reverted to normal, but no SWD ever occurred. . Moreover, drugs such as THIP, GBL or PTZ, which usually induce SWD in non-epileptic rats and potentiate SWD in the epileptic strain, (Marescaux et aI., 1984, 1990) never produced SWD on the lesioned side, whereas the SWD on the unlesioned side were markedly increased. These results clearly show that SWD cannot develop from a cortex deprived of its thalamic afferents. Moreover, cell loss, especially in pyramidal layers appears after thalamic deafferentation, which is likely to induce long-term dysfunction of the cortex. However, the clonic seizure induced by a higher dose of PTZ is expressed normally on the deafferented cortex, confirming that different substrates are involved in the various types of seizures induced by increasing doses of PTZ. None of the anterior nuclei of the thalamus appeared necessary to the occurrence of SWD. These nuclei have distinct connections from other thalamic areas: they do not receive afferents from the thalamic reticular nucleus, whereas they are innervated by a heavy projection from the mamillary body through the mamillothalamic tract (Jones, 1985). The mamillothalamic system has been involved in the propagation of convulsive seizures induced by PTZ (Mirski and Ferendelli, 1986, 1987). But this substrate appears unnecessary for the occurrence and propagation of the SWD, which can be recorded from cortex in rats with lesions of all the anterior thalamic nuclei and/or bilateral interruption of the mamillothalamic tract. Moreover, the SWD are not recorded in the anterior thalamic nuclei (Vergnes et aI., 1990). Similarly, the ventromedial nuclei and the surrounding areas are not necessary for the generation of SWD, which occur with normal frequency and amplitude after lesions of the ventromedial thalamus. The ventromedial nucleus receives a qABAergic projection from the substantia nigra (Di Chiara et aI., 1979). Our results suggest that this pathway is not involved in the nigral control of SWD (Depaulis et aI., 1990).

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The midline nuclei of the thalamus were necessary neither for the occqrrence, nor for the bilateral synchronization of the SWD. No SWD are recorded in these nuclei during absence seizures (Vergnes et al., 1987). However, SWD were elicited by electrical stimulation of the intralaminar and medial nuclei in the cat (Hunter and Jasper, 1949). These results suggested that these nuclei might, in some way, be involved in the genesis of bilateral synchronous SWD. However, it is unlikely that the spontaneous SWD in the rat are triggered from these structures. Thalamic lesions in the model of generalized penicillin epilepsy in the cat produced effects very similar to our own results in GAERS: only large lesions of the lateralis posterior nuclear group abolished the SWD, whereas lesions of the anterior nuclei, the massa intermedia or the ventromedial thalamus did not suppress penicillin-induced seizures (Pellegrini and Gloor, 1979). Altogether, these results confirm that the cortex and the thalamus are both intimately involved in the genesis of SWD in petit-mal epilepsy. More precisely, it appears that the thalamic relay nuclei are necessary for SWD to occur. These nuclei are characterized by their reciprocal connectivity with the cortex: corticothalamic connections return from every cortical area to the thalamic nuclei, providing input to that area (Jones, 1985). This organization in a closed loop may furnish the substrate allowing an oscillatory activity, possibly originating in the thalamus, to be amplified and expressed as spike and waves. En route, the cortico-thalamic fibers give collaterals to the reticular nucleus, which, in tum projects GABAergic efferents on most of the thalamic neurons, thus modulating their activity and possibly controlling their ability to discharge with rhythmic bursts (Steriade and Deschenes, 1984). The function of the thalamic reticular nucleus in the control of SWD has to be further investigated. Whether the generation of SWD is the result of an excessive cortical excitability, as was proposed in regard to feline generalized penicillin epilepsy (Gloor et al., 1979) or of an inhibitory, possibly GABAergic activity, as the primary event (Fromm, 1986) remains debatable. Acknowledgements Special thanks are given to A. Boehrer for technical assistance. This work was supported by grants from INSERM (Contrat de Recherche exteme n° 866017 and CAR n° 400019) and from "La Fondation pour la Recherche Medicale".

References Avoli M, Gloor P (1982) Interaction of cortex and thalamus in spike and wave discharges of feline generalized penicillin epilepsy. Exp Neurol 76: 196-217

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Avoli M, Gloor P, Kostopoulos G, Gotman J (1983) An analysis of penicillin-induced generalized spike and wave discharges using simultaneous recordings of cortical and thalamic single neurons. J Neurophysiol 50: 819-837 Bures J, Buresova 0, Krivanek J (1974) The mechanism and application of Leao's spreading depression of electroencephalographic activity. Publishing House of the Academy of Sciences, Prague, p 399 Depaulis A, Bourguignon JJ, Marescaux C, Vergnes M, Schmitt M, Micheletti G, Warter JM (1988) Effects of gamma-hydroxybutyrate and gamma-butyrolactone derivatives on spontaneous generalized non-convulsive seizures in the rat. Neuropharmacology 27: 683-689 Depaulis A, Vergnes M, Liu Z, Kempf E, Marescaux C (1990) Involvement of the nigral output pathways in the inhibitory control of the substantia nigra over generalized non-convulsive seizure in the rat. Neurosciences 39: 339-349 Di Chiara G, Porceddu ML, Morelli M, Mulas ML, Gessa GL (1979) Evidence for a GABAergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat. Brain Res 176: 273-284 Fromm G (1986) Role of inhibitory mechanisms in staring spells. J Clin Neurophysiol 3: 297-311 Gloor P, Pelligrini A, Kostopoulos GK (1979) Effects of changes in cortical excitability upon the epileptic bursts in generalized penicillin epilepsy of the cat. Electroencephalogr Clin Neurophysiol 46: 274-289 Hunter J, Jasper HH (1949) Effects of thalamic stimulation in unanesthetized animals. EEG Clin Neurophysiol 1: 305-324 Jones EG (1985) The thalamus. Plenum, New York, p 935 Marescaux C, Micheletti G, Vergnes M, Depaulis A, Rumbach L, Warter JM (1984) A model of chronic spontaneous petit mal-like seizures in the rat: comparison with . pentylenetetrazol-induced seizures. Epilepsia 25: 326-331 Marescaux C, Vergnes M, Depaulis A, Micheletti G, Warter JM (1992) Neurotransmission in rats' spontaneous generalized nonconvulsive epilepsy. In: Avanzini G, et al (eds) Neurotransmitters in epilepsy. Epilepsy Res [Suppl] (in press) McLachlan RS, Gloor P, Avoli M (1984) Differential participation of some "specific" and "non-specific" thalamic nuclei in generalized spike and wave discharges of feline generalized penicillin epilepsy. Brain Res 307: 277-287 Mirski MA, Ferrendelli JA (1986) Anterior thalamic mediation of generalized pentylenetetrazol seizures. Brain Res 399: 212-223 Mirski MA, Ferrendelli JA (1987) Interruption of the connections of the mammillary bodies protects against generalized pentylenetetrazol seizures in guinea pigs . . J Neurosci 7: 662-670 Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, New York Pellegrini A, Gloor P (1979) Effects of bilateral partial diencephalic lesions on cortical epileptic activity in generalized penicillin epilepsy in the cat. Exp Neural 66: 285-308 Ross DT, Ebner FF (1990) Thalamic retrograde degeneration following cortical injury: . an excitotoxic process? Neuroscience 35: 525-550 Steriade M, Deschenes M (1984) The thalamus as a neuronal oscillator. Brain Res Rev 8: 1-63 Vergnes M, Marescaux C, Micheletti G, Reis J, Depaulis A, Rumbach L, Warter JM (1982) Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized nonconvulsive epilepsy. Neurosci Lett 33: 97-101 Vergnes M, Marescaux C, Micheletti G, Depaulis A, Rumbach L, Warter JM (1984) Enhancement of spike and wave discharges by GABAmimetic drugs in rats with spontaneous petit mal-like epilepsy. Neurosci Lett 44: 91-94

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Vergnes M, Marescaux C, Depaulis A, Micheletti G, Warter JM (1987) Spontaneous spike and wave discharges in thalamus and cortex in a rat model of genetic petit mal-like seizures. Exp Neurol 96: 127-136 Vergnes M, Marescaux C, Lannes B, Depaulis A, Micheletti G, Warter JM (1989) Interhemispheric desynchronisation of spontaneous spike-wave discharges by corpus callosum transection in rats with petit mal-like epilepsy. Epilepsy Res 4: 8-13 Vergnes M, Marescaux C, Depaulis A, Micheletti G, Warter JM (1990) Spontaneous spike-and-wave discharges in Wistar rats: a model of genetic generalized nonconvulsive epilepsy. In: Avoli M, Gloor P, Kostopoulos G, Naquet R (eds) Generalized epilepsy: neurobiological approaches. Birkhauser, Boston, pp 238-253 Vergnes M, Marescaux C, Depaulis A (1990) Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized nonconvulsive epilepsy. Brain Res 523: 87-91 Warter JM, Vergnes M, Depaulis A, Tranchant C, Rumbach L, Micheletti G, Marescaux C (1988) Effects of drugs affecting dopaminergic neurotransmission in rats with spontaneous petit mal-like seizures. Neuropharmacology 27: 269-274 Williams D (1953) A study of thalamic and cortical rhythms in petit mal. Brain 76: 50-69 Authors' address: Dr. M. Vergnes, LNBC, Centre de Neurochimie du CNRS, 5, rue Blaise Pascal, F-67084 Strasbourg Cedex, France

Cortical and thalamic lesions in rats with genetic absence epilepsy.

In generalized, non-convulsive, absence epilepsy, spike-and-wave discharges (SWD) are recorded in both the cortex and the thalamus. The effect of vari...
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